Topically applied DNA vaccines may provide a safe, easy, needle-less, and cost-effective means of eliciting immunity, and has significant potential to improve world health. Recent data indicate that various skin cells can be transfected following a topical application of naked DNA. Specific immunity to DNA-encoded antigens has been observed, although the immune response following cutaneous administration has been less robust than either IM vaccination protocols or recombinant protein vaccines. Hence, commercialization of this technology is limited by technical constraints in gene transfer efficiency. Copernicus Therapeutics has developed a non-viral gene delivery technology that compacts single plasmid DNA molecules into 20-25 nm particles, termed PLASmin(TM) complexes. Our formulation is simple and reproducible, and PLASmin(TM) complexes readily transfect non-dividing, post-mitotic human cells. Our formulations are stable in normal saline and serum, and highly resistant to nuclease digestion. PLASmin(TM) complexes are stable for months and can be concentrated to approximately 7 mg/ml without loss of stability or integrity. To determine if PLASmin(TM) complexes can improve gene transfer results, several formulations will be applied to murine skin, and antibody responses to encoded antigens will be assessed. If successful, optimized PLASmin(TM) complexes will be used in a Phase II SBIR application to vaccinate humans against hepatitis. PROPOSED COMMERCIAL APPLICATION: Although naked DNA applied to skin has the potential to elicit an immune response, limitations in gene expression may hinder commercial development. Copernicus has developed a novel, non-viral technology in which single molecules of DNA are condensed with polycationic proteins. This formulation greatly improves gene transfer results in vitro and in preclinical models. If our formulation can elicit robust immunity in mice following topical application, then this DNA vaccine platform could be used to develop many products for infectious disease and cancer indications.